Salmonellosis continues to be a major worldwide health concern. Essential to the pathogenicity of these bacteria is the coordinated activities of two type III protein secretion systems (TTSS), which direct the translocation into host cells of a battery of bacterial effector proteins that modulate a variety of cellular processes. Work in our laboratory supported by this Grant has focused on the study of the cell biology of the complex functional interface between Salmonella enterica and host cells, and in particular the study of the function of several Salmonella TTSS effector proteins. This research project is aimed at deepening our understanding of the cell biology of the Salmonella/host interactions, and the function of TTSS effector proteins whose role in the infection process is poorly understood. It is hoped that these studies will facilitate the development of novel immunological and pharmacological strategies to prevent diseases caused by all Salmonella enterica serovars. Furthermore, the paradigms of host-pathogen interactions established by these studies may also help the understanding of the pathogenesis of other important pathogens, which have evolved close associations with their hosts. PUBLIC HEALTH RELEVANCE: Salmonella enterica, which causes food poisoning and typhoid fever in humans, continues to be a very significant health problem. It is estimated that there are 1.3 billion cases of Salmonella infections every year leading to 3 million annual deaths. Knowledge gained from this research should help develop novel therapeutic and prevention strategies.